crossing96/oncoscreening huggingface dataset:
Definition and Diagnosis of Oligometastatic Bladder Cancer: A Delphi Consensus Study Endorsed by the European Association of Urology, European Society for Radiotherapy and Oncology, and European Society of Medical Oncology Genitourinary Faculty.	"BACKGROUND: In contrast to other cancers, the concept of oligometastatic disease (OMD) has not been investigated in bladder cancer (BC). OBJECTIVE: To develop an acceptable definition, classification, and staging recommendations for oligometastatic BC (OMBC) spanning the issues of patient selection and the roles of systemic therapy and ablative local therapy. DESIGN, SETTING, AND PARTICIPANTS: A European consensus group of 29 experts, led by the European Association of Urology (EAU), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Medical Oncology (ESMO), and including members from all other relevant European societies, was established. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A modified Delphi method was used. A systematic review was used to build consensus questions. Consensus statements were extracted from two consecutive surveys. The statements were formulated during two consensus meetings. Agreement levels were measured to determine if consensus was achieved (≥75% agreement). RESULTS AND LIMITATIONS: The first survey included 14 questions and the second survey had 12. Owing to a considerable lack of evidence, which was the major limitation, definition was limited in the context of de novo OMBC, which was further classified as synchronous OMD, oligorecurrence, and oligoprogression. A maximum of three metastatic sites, all resectable or amenable to stereotactic therapy, was proposed as the definition of OMBC. Pelvic lymph nodes represented the only ""organ"" not included in the definition of OMBC. For staging, no consensus on the role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography was reached. A favourable response to systemic treatment was proposed as the criterion for selection of patients for metastasis-directed therapy. CONCLUSIONS: A consensus statement on the definition and staging of OMBC has been formulated. This statement will help to standardise inclusion criteria in future trials, potentiate research on aspects of OMBC for which consensus was not achieved, and hopefully will lead to the development of guidelines on optimal management of OMBC. PATIENT SUMMARY: As an intermediate state between localised cancer and disease with extensive metastasis, oligometastatic bladder cancer (OMBC) might benefit from a combination of systemic treatment and local therapy. We report the first consensus statements on OMBC drawn up by an international expert group. These statements can provide a basis for standardisation of future research, which will lead to high-quality evidence in the field."	bladder
Camrelizumab as adjuvant therapy in urothelial carcinomas after radical surgery in people living with HIV.	BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective strategies for multiple cancers and may be safe in people living with HIV (PLWH). Camrelizumab is a monoclonal antibody against PD-1 activating T cells against tumor cells. Evidence of camrelizumab's safety and activity in PLWH with urothelial carcinoma (UC) is lacking. Here, findings in a cohort of people living with HIV with advanced or metastatic urothelial carcinoma are presented. METHODS: Patients who had locally advanced or metastatic disease after radical surgery were given camrelizumab (200 mg intravenously every 3 weeks). The primary endpoint was objective response per Response Evaluation Criteria in Solid Tumors version 1.1. The second endpoint was adverse events after treatment. RESULTS: In total, nine patients were included in this study with a median follow-up of 6.2 months (4.1-20.5). The objective response rate achieved 55%. Tumor response comprised 2 (22%) complete responses and 3 (33%) partial responses. The median of progression-free survival was 6.2 months (95% CI, 9.83-20.63). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). CONCLUSION: Camrelizumab showed potent antitumor activity and acceptable safety in PLWH with advanced or metastatic urothelial carcinoma.	bladder
The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy.	Bladder cancer is one of the common malignant urothelial tumors. Post-translational modification (PTMs), including ubiquitination, acetylation, methylation, and phosphorylation, have been revealed to participate in bladder cancer initiation and progression. Ubiquitination is the common PTM, which is conducted by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin-protein ligase. E3 ubiquitin ligases play a key role in bladder oncogenesis and progression and drug resistance in bladder cancer. Therefore, in this review, we summarize current knowledge regarding the functions of E3 ubiquitin ligases in bladder cancer development. Moreover, we provide the evidence of E3 ubiquitin ligases in regulation of immunotherapy in bladder cancer. Furthermore, we mention the multiple compounds that target E3 ubiquitin ligases to improve the therapy efficacy of bladder cancer. We hope our review can stimulate researchers and clinicians to investigate whether and how targeting E3 ubiquitin ligases acts a novel strategy for bladder cancer therapy.	bladder
Atypical Oncologic Failure After Laparoscopic Radical Nephroureterectomy in a Japanese Multicenter Study.	Objectives: To investigate the recurrence patterns and the atypical oncologic failure (AOF) defined as the presence of atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, after laparoscopic radical nephroureterectomy (LRNU). Methods: LRNU performed at three institutions were included in this retrospective study. The primary endpoints were the first recurrence site and recurrence-free survival. The recurrence sites were classified as atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, as well as distant, local, and intravesical. The Kaplan-Meier curves were obtained to elucidate the time until recurrence and survival. Results: A total of 283 patients were included in the final analysis. Postoperative pathology was T3 or higher in 112 (40%) patients. The median follow-up period was 31 months, and the 3-year recurrence-free, cancer-specific, and overall survival rates were 69.6%, 78.1%, and 72.0%, respectively. The first recurrence sites involved distant, local, atypical, and intravesical recurrences in 51 (18%), 36 (13%), 14 (5%), and 94 (33%) patients, respectively. Of the 14 patients with AOF, 12 had pathologically locally advanced tumors, but seven patients had a preoperative diagnosis of clinical stage T2 or less. Conclusion: A small number of AOF cases were found after LRNU for patients with upper tract urothelial carcinoma. Careful patient selection is critical for AOF prevention.	bladder
Patterns of Utilization and Outcomes of Perioperative Chemotherapy in Patients With Locally Advanced-urothelial Bladder Cancer (LABC)-Real World Data From an Indian Tertiary Care Cancer Center.	AIM: Optimal utilization of perioperative systemic therapy in locally advanced bladder cancer (LABC) holds the key in improving the survival outcomes. We aim to analyze the oncological outcomes of clinically locally advanced urothelial bladder cancer patients treated with neoadjuvant (NACT) or adjuvant chemotherapy or without any systemic therapy in the perioperative period of radical cystectomy. METHODS & MATERIAL: We retrospectively analyzed the medical records of patients with cancer of the urinary bladder diagnosed between 2012 and 2020. The demographic profile, and the treatment received, was recorded for all patients. Oncological outcomes of the patients based on these variables were analyzed. RESULTS: Two hundred and twenty nine (229) locally advanced bladder cancer patients were included in the study. Eighty eight (38%) of them underwent upfront radical cystectomy and 141 (62%) received neoadjuvant chemotherapy (NACT). With a median follow-up of 27 months, the 2-year DFS in either of the groups was 65.4% and 67.1% respectively (P - 0.373). In the multivariate analysis, the pathological lymph nodal status and lymph vascular invasion (LVI) status influenced the DFS. The initial modality of management chosen did not affect the outcome. (HR - 0.688; 95% CI: 0.38-1.21). The commonest reason for not receiving NACT was Cisplatin ineligibility due to malignant obstructive uropathy and a subgroup analysis of this set of patients also did not show any significant difference in 2 year DFS compared to those who received NACT. CONCLUSION: A significant proportion of patients with LABC are unable to receive the recommended neoadjuvant chemotherapy and obstructive uropathy is the commonest reason for this in our centre. In our single centre series upfront radical cystectomy followed by adjuvant platinum based therapy had an outcome similar to neoadjuvant chemotherapy in LABC patients, in patients who were unable to receive the same due to various reasons.	bladder
Clock gene NR1D1 might be a novel target for the treatment of bladder cancer.	PURPOSE: To explore the role of circadian clock gene NR1D1 (REV-erbα) in bladder cancer (BC). METHODS: Firstly, the association of NR1D1 level with clinical characteristics and prognosis was investigated among patients diagnosed with BC. Secondly, CCK-8, transwell, and colony formation experiments were performed among BC cells treated with Rev-erbα agonist (SR9009), as well as lentivirus and siRNA, for which NR1D1 were overexpressed (OE) and knocked down (KD), respectively. Thirdly, cell cycle and apoptosis were tested by flowcytometry. PI3K/AKT/mTOR pathway proteins were determined in OE-NR1D1 cells. Finally, OE-NR1D1 and OE-Control BC cells were subcutaneously implanted in BALB/c nude mice. The tumor size and protein levels were compared between groups. A P < 0.05 was considered as statistically significant. RESULTS: Patients with NR1D1 positive status had a longer disease-free survival than those with negative expression. The cell viability, migration, and colony formation of BC cells after treated with SR9009 were significantly suppressed. OE-NR1D1 cells had obviously inhibited cell viability, migration, and colony formation, while those were found strengthened in KD-NR1D1 cells. Besides, KD-NR1D1 cells were observed with a lower proportion of dead cells and G0/G1 cells, but a higher ratio of G2/M. The changes of p-AKT, p-S6, p-4EBP1, and FASN involved in PI3K/AKT/mTOR pathway were detected in OE- and KD-NR1D1 BC cells. Finally, in vivo data demonstrated that overexpression of NR1D1 suppressed the tumorigenicity of BC cells. CONCLUSION: NR1D1 played a role of tumor suppressor and it might become a novel target for the treatment of BC.	bladder
Adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible high-risk bladder cancer patients: Long-term follow-up of a randomized phase 3 trial.	BACKGROUND: Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. METHODS: High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3-11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57-1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2-56.2) and 30.4% (95% CI: 19.0-42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49-1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8-49.7) in the adjuvant group and 22.2% (95% CI: 11.5%-35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. CONCLUSIONS: There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.	bladder
Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors.	CONTEXT: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE: To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION: Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS: Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS: We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY: Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer.	bladder
Increased Burden of Second Bladder Cancer and Rectal Cancer in Prostate Cancer Treated With Radiotherapy: Results From Surveillance, Epidemiology, and End Results.	BACKGROUND: Previous studies have confirmed the higher risk of bladder cancer (BC) and rectal cancer (RC) development among prostate cancer (PCa) patients receiving radiotherapy. In this study, we intend to explore the long-term trend in second BC and RC incidence among PCa patients undergoing radiotherapy. METHOD: We identified first primary PCa patients diagnosed between 1975 and 2014 from the Surveillance, Epidemiology, and End Results (SEER)-9 cancer registries. Standardized incidence ratios (SIRs) were calculated by calendar year of diagnosis among PCa patients receiving radiotherapy and not. P trends were evaluated using Poisson regression. 10-year cumulative incidence of BC and RC was calculated utilizing competing risk regression model. RESULT: Of PCa patients treated with radiotherapy, SIRs of BC increased from .82 (95% CI: .35- 1.61) in 1980-1984 to 1.58 (95% CI: 1.48-1.68) in 2010-2014 (Ptrend=.003). SIRs of RC increased from 1.01 (95% CI: .27-2.58) in 1980-1984 to 1.54 (95% CI: 1.31-1.81) in 2010-2014 (Ptrend=.025). No statistically significant change in both BC and RC incidence was observed. The 10-year cumulative incidence of BC increased from 1975-1984 (.04%) to 2005-2014 (.15%) among PCa treated with radiotherapy. Simultaneously, the 10-year cumulative incidence of RC was demonstrated to range from 1975-1984 (.02%) to 2005-2014 (.11%). CONCLUSION: we have observed an increasing trend in second BC and RC incidence in PCa patients receiving radiotherapy. There was no significant change in the incidence of second BC and RC in PCa without radiotherapy. These results reflect the increasing clinical burden of second malignant tumors in PCa patients undergoing radiotherapy.	bladder
The accuracy of cystoscopy in predicting muscle invasion in newly diagnosed bladder cancer patients.	PURPOSE: The prognosis of muscle-invasive bladder cancer (MIBC) has not improved for three decades. Transurethral resection of the bladder tumor (TURBT) is the standard procedure for local tumor staging. TURBT has several limitations, including the spread of tumor cells. Therefore, an alternative is needed in patients with suspected MIBC. Recent studies have shown that mpMRI is very accurate in staging bladder tumors. Because the diagnostic efficacy of urethrocystoscopy (UCS) has been reported as good as the efficacy of mpMRI to predict muscle invasion we performed this prospective multicenter study in which we compare UCS with pathology. METHODS: From July 2020 until March 2022, 321 patients with suspected primary BC in seven participating Dutch hospitals were included in this study. A flexible UCS was performed by urologists, physician assistants, or residents. Predictions of muscle invasion using a 5-point Likert scale alongside the histopathology data were recorded. The sensitivity, specificity, predictive values, and 95% confidence intervals were determined using a standard contingency table. RESULTS: Of the 321 included patients, 232 (72.3%) received a histopathological diagnosis of non-muscle-invasive bladder cancer (NMIBC) and 71 (22.1%) were histopathologically diagnosed as MIBC. In 2 patients (0.6%), classification was not possible (Tx). Cystoscopy predicted muscle invasion with a sensitivity of 71.8% (95% CI 59.9-81.9), and a specificity of 89.9% (95% CI 85.4-93.3). This corresponds to a positive predictive value (PPV) of 67.1% and a negative predictive value (NPV) of 91.7%. CONCLUSION: Our study shows a moderate accuracy of cystoscopy to predict muscle invasion. This result does not support the use of cystoscopy only instead of TURBT for local staging.	bladder
Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea.	IMPORTANCE: The antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored. OBJECTIVE: To assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023. EXPOSURE: Newly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled. MAIN OUTCOMES AND MEASURES: The primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis. RESULTS: The study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group. CONCLUSIONS AND RELEVANCE: Results of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.	bladder
Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC).	To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001-September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator's choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population.	bladder